Browsing by Author "Miranda Saavedra, Diego"

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    Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites
    (eLife Sciences Publications Ltd, 2015) Woo, Yong; Ansari, Hifzur; Otto, Thomas; Linger, Christen; Olisko, Martin; Michálek, Jan; Saxena, Alka; Shanmugam, Dhanasekaran; Tayyrov, Annageldi; Veluchamy, Alaguraj; Ali, Shajahan; Bernal, Alex; Campo, Javier del; Cihlár, Jaromir; Flegontov, Pavel; Gornik, Sebastian; Hajdušková, Eva; Horák, Ales; Janouškovec, Jan; Katris, Nicholas; Mast, Fred; Miranda Saavedra, Diego; Mourier, Tobias; Naeem, Raeece; Nair, Mridul; Panigrahi, Aswini; Rawlings, Neil; Padron Regalado, Eriko; Ramaprasad, Abhinay; Samad, Nadira; Tomcala, Ales; Wilkes, Jon; Neafsey, Daniel; Doerig, Christian; Bowler, Chris; Keeling, Patrick; Roos, David; Dacks, Joel; Templeton, Thomas; Waller, Ross; Lukeš, Julius; Oborník, Miroslav; Pain, Arnab; https://ror.org/02jjdwm75
    The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites of humans and animals with immense socio-economic and health impacts. We sequenced nuclear genomes of Chromera velia and Vitrella brassicaformis,free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways and from the endomembrane trafficking systems associated with a free-living lifestyle have been progressively and non-randomly lost during adaptation to parasitism. The free-living ancestor contained a broad repertoire of genes many of which were repurposed for parasitic processes,such as extracellular proteins,components of a motility apparatus,and DNA- and RNA-binding protein families. Based on transcriptome analyses across 36 environmental conditions,Chromera orthologs of apicomplexan invasion-related motility genes were co-regulated with genes encoding the flagellar apparatus,supporting the functional contribution of flagella to the evolution of invasion machinery. This study provides insights into how obligate parasites with diverse life strategies arose from a once free-living phototrophic marine alga. © Woo et al.
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    Genomic analysis of LPS-stimulated myeloid cells identifies a common pro-inflammatory response but divergent IL-10 anti-inflammatory responses
    (Nature Publishing Group, 2015) Hutchins, Andrew Paul; Takahashi, Yoshiko; Miranda Saavedra, Diego; Japan Society for the Promotion of Science; National Natural Science Foundation of China; China Postdoctoral Science Foundation; https://ror.org/02jjdwm75
    Inflammation is an essential physiological response to infection and injury that must be kept within strict bounds. The IL-10/STAT3 anti-inflammatory response (AIR) is indispensable for controlling the extent of inflammation,although the complete mechanisms downstream of STAT3 have not yet been elucidated. The AIR is widely known to extend to other myeloid cells,but it has best been characterized in macrophages. Here we set out to characterize the LPS-mediated pro-inflammatory response and the AIR across a range of myeloid cells. We found that whereas the LPS-induced pro-inflammatory response is broadly similar among macrophages,dendritic cells,neutrophils,mast cells and eosinophils,the AIR is drastically different across all myeloid cell types that respond to IL-10 (all bar eosinophils). We propose a model whereby the IL-10/STAT3 AIR works by selectively inhibiting specific pathways in distinct cell types: in macrophages the AIR most likely works through the inhibition of NF-?B target genes; in DCs and mast cells through indirect IRF disruption; and in neutrophils through IRF disruption and possibly also indirect NF-?B inhibition. In summary,no conserved IL-10/STAT3 AIR effectors were identified; instead a cell type-specific model of the AIR is proposed. © 2015,Nature Publishing Group. All rights reserved.